Pycnogenol is an extract derived from the bark of the maritime pine (Pinus pinaster), which is native to the Mediterranean region and is attributed antioxidant and anti-inflammatory properties. The MMI Pharmindex lists 18 products classified as non-prescription dietary supplements containing between 30 and 100 mg of Pycnogenol.
The present literature review (see Appendix 1) examined whether this plant-derived compound may exert potential therapeutic effects in inflammatory rheumatic diseases. [1] Despite a targeted search for studies on rheumatoid arthritis (RA), no relevant publication was identified; instead, only studies on Sjögren syndrome, systemic lupus erythematosus (SLE), lupus vasculitis, and Behçet syndrome were found [1] [2] [3] [4] [5].
The identified studies describe positive effects of Pycnogenol. Luzzi et al. reported a significant reduction in erythrocyte sedimentation rate and an improvement in clinical symptoms in Sjögren syndrome [4]. In an open-label registry study with a mixed cohort of patients with SLE, Behçet syndrome, Sjögren syndrome, and polyarteritis nodosa, Belcaro et al. found a significant reduction in interleukin-6 as well as decreased use of glucocorticoids and nonsteroidal anti-inflammatory drugs in the Pycnogenol group [1]. Further studies in patients with systemic lupus and vasculitis documented improvements in parameters such as photosensitivity, oral ulceration, significantly lower autoantibody titers against double-stranded DNA, and fewer cases of thrombocytopenia [2]. A critical limitation of the study by Cesarone et al. is that no classification criteria were used to define systemic lupus and vasculitis [2]. In addition, one study demonstrated a significant reduction in oxidative stress and disease activity in SLE [5].
Furthermore, studies with small sample sizes and short treatment duration found a significant reduction in pain in knee osteoarthritis [6] [7] [8]. These findings may also be extended to hand osteoarthritis [9]. At the same time, a reduction in the use of analgesic medication was observed [6] [7]. Improvements in grip strength in hand osteoarthritis and walking distance in knee osteoarthritis were also reported [9] [7].
Based on these small studies with limited patient numbers, it may be discussed whether a beneficial effect on disease activity could exist in systemic lupus erythematosus, Behçet syndrome, and Sjögren syndrome. With regard to the treatment of osteoarthritis, Pycnogenol was associated with a reduction in osteoarthritis-related pain.
It must be emphasized critically that the studies have significant methodological deficiencies. The investigations were open-label, uncontrolled, and based on small sample sizes, which substantially limits the strength of the conclusions. The endpoints used—mostly nonspecific inflammatory markers or subjective symptom scales—also do not permit a robust assessment of clinical relevance. [1]. No comparative studies with established disease-modifying drugs are available. Furthermore, adverse effects are not discussed.
There are currently insufficient data to support the use of Pycnogenol for the treatment of inflammatory rheumatic diseases. Studies with clearly defined clinical endpoints would be required to enable a sound evaluation.
If patients with osteoarthritis explicitly request a phytotherapeutic supplement in addition to an established treatment concept, Pycnogenol may be mentioned as an option for self-medication. However, the weak level of evidence should be clearly communicated.
References
1. Belcaro G, Hu S, Cesarone MR, Scipione V, Scipione C, Dugall M, Cornelli U, Cox D, Hosoi M, Feragalli B et al: Supplementation with Pycnogenol® relieves symptoms of chronic inflammatory diseases with a significant vasculitis component: a pilot registry study. Minerva Med 2025, 116(2):106-112.
2. Cesarone MR, Belcaro G, Corsi M, Scipione C, Scipione V, Hu S, Hosoi M, Ledda A, Feragalli B, Cotellese R: Supplementary management with Pycnogenol® in patients with lupus vasculitis in remission phases: a pilot, concept registry study. Minerva Cardioangiol 2020, 68(2):146-152.
3. Hu S, Belcaro G, Ledda A, Corsi M, Cotellese R, Feragalli B, Hosoi M, Dugall M, Torino-Rodriguez P, Cesarone MR: Behçet syndrome: effects of Pycnogenol® supplementation during regression phases. Minerva Cardioangiol 2018, 66(4):386-390.
4. Luzzi R, Belcaro G, Hu S, Feragalli B, Hosoi M, Dugall M, Ledda A: Efficacy of Pycnogenol® supplementation in remission phases of Sjögren syndrome. Minerva Cardioangiol 2018, 66(5):543-546.
5. Stefanescu M, Matache C, Onu A, Tanaseanu S, Dragomir C, Constantinescu I, Schönlau F, Rohdewald P, Szegli G: Pycnogenol efficacy in the treatment of systemic lupus erythematosus patients. Phytother Res 2001, 15(8):698-704.
6. Feragalli B, Dugall M, Luzzi R, Ledda A, Hosoi M, Belcaro G, Cesarone MR: Pycnogenol®: supplementary management of symptomatic osteoarthritis with a patch. An observational registry study. Minerva Endocrinol 2019, 44(1):97-101.
7. Belcaro G, Cesarone MR, Errichi S, Zulli C, Errichi BM, Vinciguerra G, Ledda A, Di Renzo A, Stuard S, Dugall M et al: Treatment of osteoarthritis with Pycnogenol. The SVOS (San Valentino Osteo-arthrosis Study). Evaluation of signs, symptoms, physical performance and vascular aspects. Phytother Res 2008, 22(4):518-523.
8. Jessberger S, Högger P, Genest F, Salter DM, Seefried L: Cellular pharmacodynamic effects of Pycnogenol® in patients with severe osteoarthritis: a randomized controlled pilot study. BMC Complement Altern Med 2017, 17(1):537.
9. Cesarone MR, Belcaro G, Cox D, Scipione V, Scipione C, Dugall M, Hosoi M, Feragalli B, Hu S, Coppazuccari F et al: Supplementary management of symptomatic hand osteoarthritis with Pycnogenol®. Minerva Surg 2024, 79(5):539-544.
Appendix 1: Assessment of the evidence base: design of the PubMed search.
| Keywords | References identified in PubMed |
|---|---|
| pycnogenol rheumatic or pycnogenol arthritis | n = 1 |
| pycnogenol and vasculitis rheumatic | n = 0 |
| pycnogenol and vasculitis rheumatoid | n = 0 |
| pycnogenol and connective tissue disease | n = 3 |
| pycnogenol and psoriatic arthritis | n = 0 |
| pycnogenol and spondyloarthritis | n = 0 |
| pycnogenol and systemic sclerosis | n = 0 |
| pycnogenol and sharp sydrome | n = 0 |
| pycnogenol and sjögren syndrome | n = 2 |
| pycnogenol and lupus | n = 3 |
| pycnogenol and giant cell arteriitis | n = 0 |
| pycnogenol and arteriitis temporalis | n = 0 |
| pycnogenol and panarteriitis nodosa | n = 1 |
| pycnogenol and granulomatosis with polyangiitis | n = 0 |
| pycnogenol and osteoarthritis | n = 4 |
| pycnogenol and microscopic polyangiitis | n = 0 |
| pycnogenol and eosinophilic granulomatosis with polyangiitis | n = 0 |
| pycnogenol and Morbus Bechet | n = 1 |
| pinus pinaster rheumatic or pinus pinaster arthritis | n = 0 |
| pinus pinaster and vasculitis rheumatoid | n = 0 |
| pinus pinaster and connective tissue disease | n = 0 |
| pinus pinaster and osteoarthritis | n = 0 |
Duplicate studies were excluded from the analysis. [1] Animal studies and reviews were likewise excluded.
Appendix 2: Overview of the evaluated publications.
| Publikation | Kollektiv | Ergebnisse |
|---|---|---|
| Luzzi R et al. [4] |
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| Belcaro G et al. [1] |
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| Cesarone MR et al. [2] |
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| Stefanescu et al. [5] |
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| Hu et al. [3] |
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| Cesarone et al. [9] |
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| Feragalli et al. [6] |
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| Jessberger et al. [8] |
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| Belcaro et al. [7] |
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Last updates: March 11, 2026